In cardiac surgery patients does Voluven(R) impair coagulation less than other colloids?

Hydroxyethyl starch (HES) solutions are commonly used for volume replacement in cardiac surgery patients. The degree of impairment of the haemostatic system depends on the molecular weight and substitution degree of HES solutions. It is claimed that as HES 130/0.4 (Voluven(?)) exhibits a lower in vitro molecular weight and a lower degree of hydroxyethyl substitution than HES 200/0.5 (HAES-steril(?)) therefore it has less impact on haemostasis. A best evidence topic in cardiac surgery was written according to a structured protocol to verify this statement. The question addressed was: in cardiac surgery patients does volume replacement with Voluven(?) impair coagulation less than other colloids? Using the reported search 12 papers, three in vitro and nine clinical studies, were found to represent the best evidence to answer the clinical question. The nine clinical studies were all randomised controlled trials. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The in vitro studies suggest that HES 130/0.4 has no significant effect on platelet variables, shows a faster clot formation process and a better clot retraction as compared with the other HES solutions. On the other hand, current best available evidence (level 1b) from clinical studies, limited by heterogeneity predominantly in terms of dosage of HES 130/0.4 administered and the sample size of individual trials, overwhelmingly suggests that HES 130/0.4 compared with HES 200/0.5 or gelatin-based volume replacement fluid affects coagulation to the same extent resulting in similar degree of blood loss. It can be concluded that contrary to in vitro studies HES 130/0.4 in clinical practice has comparable effects on blood loss after cardiac surgery.     

A novel hydroxyethyl starch (Voluven®) for effective perioperative plasma volume substitution in cardiac surgery

PURPOSE: To compare the new hydroxyethyl starch HES 130/0.4 (Voluven) and the standard HES 200/0.5 (pentastarch) regarding effectiveness for plasma volume substitution and safety of large volumes in heart surgery. METHODS: Fifty-nine patients scheduled for coronary artery bypass grafting were enrolled in a prospective, randomised, double-blind, parallel-group, multicentre, clinical, phase III study. Hydroxyethyl starch was used as the exclusive artificial colloid for acute normovolemic hemodilution, priming of the heart lung machine, and for intra- and postoperative plasma volume substitution from induction of anesthesia until 16 hr after the end of surgery. Efficacy was evaluated by comparing the amount of colloid infused, hemodynamics, and colloid osmotic pressure (COP). Safety endpoints were blood loss, the use of allogeneic blood products, coagulation variables, and adverse events. RESULTS: Effectiveness, as assessed by the total amount of infused HES volumes within the treatment period, was similar between HES 130/0.4 and HES 200/0.5 (2,550 mL +/- 561 mL vs 2,466 mL +/- 516 mL). Also, no differences were found for the use of other colloids (pasteurised plasma), hemodynamics, and COP In HES 130/0.4 patients, the postoperative increase of von-Willebrand factor (vWF) was higher (P < 0.01), blood loss was lower, and less packed red blood cells were transfused. CONCLUSION: Hydroxyethyl starch 130/0.4 is an effective plasma volume expander in heart surgery and may be used as the sole artificial colloid to cover the perioperative period. We found a reduced influence of HES 130/0.4 on the physiologic postoperative increase of vWF.     

Voluven, a lower substituted novel hydroxyethyl starch (HES 130/0.4), causes fewer effects on coagulation in major orthopedic surgery than HES 200/0.5

Hydroxyethyl starch (HES) solutions are effective plasma volume expanders. Impairment of coagulation occurs with large HES volumes infused perioperatively. Therefore, a lower substituted novel HES (Voluven; Fresenius Kabi, Bad Homburg, Germany) was developed to minimize hemostatic interactions, and was compared with HAES-steril (Fresenius Kabi) (pentastarch) regarding safety and efficacy. We performed a prospective, randomized, double-blinded study in 100 major orthopedic surgery patients. Because the 95% confidence interval (-330 mL; +284 mL) for the treatment contrast Voluven-HAES-steril was entirely included in the predefined equivalence range (+/- 500 mL), comparable efficacy was established. Voluven interfered significantly less than HAES-steril with coagulation factor VIII levels and partial thromboplastin time postoperatively. Total amounts of red blood cells transfused were comparable between the Voluven and HAES-steril groups, but a significantly reduced need for homologous red blood cells was observed in the Voluven group. We conclude that in large-blood-loss surgery, Voluven has a comparable efficacy with HAES-steril and may reduce coagulation impairment, possibly leading to a smaller number of allogeneic blood transfusions. IMPLICATIONS: Hydroxyethyl starches are common plasma volume expanders, but may interfere with coagulation at large doses. We tested a novel hydroxyethyl starch specification (Voluven; Fresenius Kabi, Bad Homburg, Germany) which was developed to reduce hemostatic interactions while preserving its efficacy in restoring plasma volume in comparison to HAES-steril (pentastarch; Fresenius Kabi) in major orthopedic surgery.     

Plasma volume changes associated with two hydroxyethyl starch colloids following acute hypovolaemia in volunteers

This randomised double blind prospective study compared the effective intravascular volume expansion and maintenance, with two types of starches following induced haemorrhagic hypovolaemia. Twenty healthy male volunteers aged between 18 and 65 year were bled 10% of their total blood volume in fully monitored conditions and under the supervision of a trained specialist doctor and research nurse. The lost blood volume was replaced using one of the starch solutions. Effective intravascular volume expansion was monitored hourly using the (51)Cr radio-labelled red blood cell dilution technique, we compared the effects of two hydroxyethyl starch colloid preparations, one a high molecular weight and the other a low molecular weight preparation, on the plasma volume changes over time. The large molecular weight starch (Hextend) provided a less well-sustained volume expansion effect than the smaller one (Voluven)     

The effects of colloid solutions on renal proximal tubular cells in vitro

Renal failure is a common complication of critically ill patients. Colloids such as hydroxyethyl starch (HES), gelatin, or albumin are regularly used for intravascular volume resuscitation, but there are increasing reports about the nephrotoxic side effects of synthetic colloids in septic patients. Therefore, we investigated the influence of colloids (HES130/0.4 (Voluven?), gelatin (Gelafundin?), human albumin, and the crystalloid Sterofundin? ISO on cell viability of human proximal tubular (HK-2) cells. HK-2 cells were incubated with colloids (0.1%-4%) and with equivalent volumes of the crystalloid solution Sterofundin ISO. After 21 hours, cell viability of HK-2 cells was measured by EZ4U assay (dye XTT). Application of HES130/0.4 decreased cell viability significantly in a concentration-dependent manner (86.80% ± 10.79% by 0.5% HES down to 24.02% ± 4.27% by 4% HES). Human albumin (>1.25%) as well as gelatin (>1%) also showed deleterious effects on HK-2 cells. Interestingly, in lower concentrations, human albumin and the crystalloid solution Sterofundin ISO were cytoprotective in comparison with the NaCl control. In conclusion, synthetic and natural colloids showed a harmful impact on HK-2 cells in higher concentrations without any prior proinflammatory stimulus. HES130/0.4 exhibited the most distinctive harmful impact, whereas the application of crystalloid Sterofundin ISO revealed cytoprotective effects.     

Volume replacement therapy during major orthopedic surgery using Voluven (hydroxyethyl starch 130/0.4) or hetastarch

BACKGROUND: The purpose of this study was to test the equivalence of efficacy and compare the safety of the 6% hydroxyethyl starches (HES) Voluven (HES 130/0.4; Fresenius Kabi, Bad Homburg, Germany) and hetastarch (HES 670/0.75 in saline) for intravascular volume replacement therapy during major orthopedic surgery. METHODS: In a prospective, controlled, randomized, double-blind, multicenter trial of patients undergoing major orthopedic surgery, 49 patients were treated with HES 130/0.4 and 51 patients were treated with hetastarch. Infusion of colloids was guided by central venous and arterial blood pressures. The primary efficacy endpoint was the volume of colloid solution infused; the primary safety endpoints were calculated total erythrocyte loss, the nadir factor VIII activity, and the nadir von Willebrand factor concentration within 2 h of completion of surgery. RESULTS: The total volume of colloid solution required for intraoperative volume replacement did not differ between HES 130/0.4 and hetastarch (1,613+/-778 [SD] ml for HES 130/0.4 and 1,584+/-958 ml for hetastarch). The nadir factor VIII activity within 2 h of the end of surgery was lower for hetastarch than for HES 130/0.4 (P=0.0499); for those who received greater than 1,000 ml colloid, the nadir factor VIII activity and von Willebrand factor concentration within 2 h of end of surgery were lower for hetastarch than for HES 130/0.4 (P=0.0487 and P=0.008, respectively). CONCLUSION: Voluven (HES 130/0.4) and hetastarch are equally efficacious plasma volume substitutes; however, HES 130/0.4 has a lesser effect on coagulation.     

Effects of intravascular volume therapy using hydroxyethyl starch (130/0.4) on post-operative bleeding and transfusion requirements in children undergoing cardiac surgery: a randomized clinical trial

BACKGROUND: Hydroxyethyl starch (HES) used for intravascular volume expansion may cause coagulation abnormalities, especially in cardiac patients. Although low molecular weight HES (130/0.4) has been developed to minimize its influence on coagulation, experience with HES (130/0.4) in children is limited. Therefore, we evaluated the effects of a HES (130/0.4) infusion on post-operative blood loss in children undergoing cardiac surgery. METHODS: Forty-two children undergoing cardiac surgery were assigned at random to receive either 10 ml/kg fresh frozen plasma (FFP group; n=21) or HES (130/0.4) (HES group; n=21) shortly after cardiopulmonary bypass termination. Activated partial thromboplastin time (aPTT) and international normalization ratio (INR) were measured. In addition, post-operative transfusion requirements and blood loss until the end of the first post-operative day were compared. RESULTS: INR was significantly prolonged after HES infusion in comparison to the FFP group (P<0.05). During the first 24 h after surgery, post-operative blood loss, the use of allogenic blood/blood products and aPTT were similar in all children. CONCLUSIONS: Our study shows that the administration of a moderate dose of HES (130/0.4) in children undergoing cardiac surgery does not cause more bleeding or a higher transfusion requirement than a FFP infusion, and suggests that the administration of 10 ml/kg HES (130/0.4) is a safe alternative to plasma for intravascular volume replacement in this patient population.     

羟乙基淀粉在脓毒症液体复苏中应用与争论

液体复苏是脓毒症治疗十分重要的基础环节,而液体种类的选择是此领域近年来的热门议题之一。最新几项多中心、随机对照研究（RCT）报道,脓毒症病人液体复苏治疗时使用羟乙基淀粉130/0.4或0.42（HES 130/0.4或0.42）可导致肾脏替代治疗（RRT）的需求及90 d 死亡风险显著增加。系统、深入地分析现有研究报告资料发现,HES 130/0.4或0.42引起急性肾损伤（AKI）的临床证据欠充分;与晶体液比较,HES 130/0.4或0.42引起脓毒症病人90 d
病死率升高的结论在不同RCT研究中存在高异质性,且此结论可能受混杂因素的影响。因此,对HES 130/0.4或0.42在脓毒症病人中应用安全性的客观评价仍有赖于进一步获得更多可靠的临床数据。     

Randomized clinical trial comparing the effects on renal function of hydroxyethyl starch or gelatine during aortic aneurysm surgery

BACKGROUND: The optimal colloid for renal protection during abdominal aortic aneurysm (AAA) surgery is not known. This study compared the effects of two hydroxyethyl starch (HES) solutions and gelatine on perioperative renal function. METHODS: Sixty-two patients undergoing AAA surgery were randomized to 6 per cent HES of molecular weight 200/0.62 kDa or 130/0.4 kDa, or 4 per cent gelatine for plasma expansion. Measurements were taken of serum urea and creatinine to mark glomerular filtration, urinary immunoglobulin G : creatinine ratio to mark glomerular membrane function and alpha(1)-microglobulin : creatinine ratio to mark tubular dysfunction before, and for 5 days after, surgery. RESULTS: Serum urea was lower in both HES groups than the gelatine group. Serum creatinine was lower with HES 130/0.4 compared with gelatine at days 1, 2 and 5 after surgery (P = 0.020, P = 0.045 and P = 0.045 respectively). Urinary alpha(1)-microglobulin : creatinine ratio was lower with HES 200/0.62 compared with gelatine at 4 and 8 h (P < 0.050) and lower with HES 130/0.4 compared with gelatine at 4 to 24 h, and on days 4 and 5 (P < 0.050). Urinary immunoglobulin G : creatinine was lower in both HES groups compared with gelatine. There was no difference between the two starch groups. CONCLUSION: Compared with gelatine, volume expansion with both types of HES during AAA surgery improved renal function and reduced renal injury.     

Novel starches: single-dose pharmacokinetics and effects on blood coagulation

BACKGROUND: Carboxymethyl starch (CMS) and carboxymethylated hydroxyethyl starch (CM-HES) might offer advantages over hydroxyethyl starch (HES) with regard to their volume expansion effect and their pharmacokinetic characteristics. The goal of the current study was to determine the pharmacokinetics of CMS and CM-HES and to investigate their influence on blood coagulation in comparison with the standard low-molecular, low-substituted HES (130/0.42) used in Europe. METHODS: The study was conducted as a randomized, blinded, parallel three-group study in 30 pigs. Twenty ml/kg of 6% HES (control), 6% CMS, or 6% CM-HES was infused as a single dose, and serial blood sampling was performed over 20 h to measure plasma concentration and molecular weight and to assess blood coagulation. Concentration-effect relations were assessed by pharmacokinetic-pharmacodynamic analysis. RESULTS: CMS and CM-HES showed significantly higher plasma concentrations and molecular weights over 20 h (P for both<0.001) with smaller volumes of distribution and longer elimination rates during the terminal phase (P for both<0.01) when compared with HES. CMS and CM-HES impaired whole blood coagulation more than HES as assessed by Thrombelastograph analysis (Haemoscope Corporation, Niles, IL). However, similar effects of all three starch preparations on blood coagulation were found when related to the plasma concentrations in mass units. CONCLUSIONS: Carboxymethylation of starch results in an increased intravascular persistence and a slower fragmentation compared with HES. The greater impairment of blood coagulation by CMS and CM-HES seems to be caused by the higher plasma concentrations.     

Changes in circulating blood volume after infusion of hydroxyethyl starch 6% in critically ill patients

BACKGROUND: The cardiovascular response to a volume challenge with hydroxyethyl starch (HES) (200/0.5) 6% depends on the relation between the volume of HES 6% infused and the expansion of the blood volume in critically ill patients. However, only relatively limited data exist on the plasma expanding effect of infusion of HES 6% in critically ill patients. The purpose of the study was to evaluate the variation in the expansion of the circulating blood volume (CBV) in critically ill patients after infusion of 500 ml of colloid (HES (200/0.5) 6%) using the carbon monoxide method. METHODS: In 20 consecutive patients admitted to the ICU requiring mechanical ventilation and volume expansion, 500 ml of HES (200/0.5) 6% was infused. The CBV was measured immediately before the infusion, 10 min after completing the infusion and then hourly for 8 h. RESULTS: The median volume expansion immediately after infusion was 470 ml (range 270 ml to 840 ml). The corresponding values after 4 h and 8 h were 265 ml (range -30 ml to 460 ml) and 120 ml (range -210 ml to 360 ml), respectively. The increase in CBV was only statistically significant for 4 h. The coefficient of variation of the method for estimation of CBV was 3.6%. CONCLUSIONS: The large interindividual variation of the volume expansion after infusion of HES 6% in critically ill patients illustrates one of the difficulties in optimizing colloid therapy and interpretating the changes in hemodynamic variables after a colloid challenge.     

Novel Starches: Single-dose Pharmacokinetics and Effects on Blood Coagulation

Background: Carboxymethyl starch (CMS) and carboxymethylated hydroxyethyl starch (CM-HES) might offer advantages over hydroxyethyl starch (HES) with regard to their volume expansion effect and their pharmacokinetic characteristics. The goal of the current study was to determine the pharmacokinetics of CMS and CM-HES and to investigate their influence on blood coagulation in comparison with the standard low-molecular, low-substituted HES (130/0.42) used in Europe.

Methods: The study was conducted as a randomized, blinded, parallel three-group study in 30 pigs. Twenty ml/kg of 6% HES (control), 6% CMS, or 6% CM-HES was infused as a single dose, and serial blood sampling was performed over 20 h to measure plasma concentration and molecular weight and to assess blood coagulation. Concentration-effect relations were assessed by pharmacokinetic-pharmacodynamic analysis.

Results: CMS and CM-HES showed significantly higher plasma concentrations and molecular weights over 20 h (P for both < 0.001) with smaller volumes of distribution and longer elimination rates during the terminal phase (P for both < 0.01) when compared with HES. CMS and CM-HES impaired whole blood coagulation more than HES as assessed by Thrombelastograph(R) analysis (Haemoscope Corporation, Niles, IL). However, similar effects of all three starch preparations on blood coagulation were found when related to the plasma concentrations in mass units.     

Effects of PentaLyte and Voluven hemodilution on plasma coagulation kinetics in the rabbit: role of thrombin-fibrinogen and factor XIII-fibrin polymer interactions

BACKGROUND: Hydroxyethyl starch (HES) administration has resulted in decreased hemostasis and fibrinogen (FI)-thrombin-(FIIa)-Factor XIII (FXIII) interactions. I proposed to determine the hemostatic effect of hemodilution with PentaLyte (6% HES, mean molecular weight 220 kDa) and Voluven (6% HES, 130 kDa). METHODS: Rabbits were intravenously administered 20 ml/kg PentaLyte or Voluven (n = 8 per fluid) over 10 min. Plasma was obtained prior to, 1 min and 1 h after hemodilution. Thrombelastography was performed, with clot initiation (R, sec), clot propagation (alpha, degrees), and clot strength (shear elastic modulus, G, dynes/cm2) determined over 20 min. Celite-activated samples had either no additions or addition of FI, FIIa or activated FXIII (FXIIIa) to restore protein content to pre-diluted values. RESULTS AND CONCLUSIONS: While there were no significant differences between the groups, R significantly decreased 1 h after hemodilution compared with values observed before and 1 min after hemodilution, whereas alpha and G significantly decreased 1 min after hemodilution and then significantly, but only partially, increased 1 h after hemodilution compared with pre-dilution values. Addition of FI, FIIa and FXIIIa significantly decreased R in both groups. alpha and G 1 min after hemodilution were significantly enhanced by FI, FIIa, FXIIIa in both groups; however, 1 h after hemodilution, rabbits administered PentaLyte had alpha and G enhanced only by FI and FXIIIa addition, whereas animals administered Voluven had alpha and G significantly enhanced by FI addition. PentaLyte and Voluven hemodilution initially diminishes FIIa-FI and FXIIIa-fibrin, but within an hour primarily inhibit FXIIIa-fibrin interactions in the rabbit.     

Repetitive large-dose infusion of the novel hydroxyethyl starch 130/0.4 in patients with severe head injury

In this prospective, controlled, randomized, single-center study, we investigated the safety of repetitive large-dose infusion of a novel hydroxyethyl starch solution (6% HES 130/0.4) in cranio-cerebral trauma patients. Patients were randomized to receive either HES 130/0.4 (n = 16) at repetitive doses of up to 70 mL x kg(-1) x d(-1) (which is the largest HES dose reported in the literature) or the control HES 200/0.5 (n = 15) up to its approved dose limit of 33 mL x kg(-1) x d(-1) followed by human albumin up to a total dose (HES 200/0.5 + albumin) of 70 mL x kg(-1) x d(-1). We found no differences between groups in mortality, renal function, bleeding complications, and use of blood products. There were also no major differences in coagulation variables. However, at some time points, factor VIII, von Willebrand factor, and ristocetin cofactor were higher in the HES 130/0.4 group despite the large HES doses administered. We conclude that HES 130/0.4 can safely be used in critically ill head trauma patients over several days at doses of up to 70 mL x kg(-1) x d(-1). IMPLICATIONS: There are concerns that infusion of certain hydroxyethyl starch (HES) types for plasma volume expansion may influence coagulation and renal function. We investigated the safety of the novel HES 130/0.4 in patients with severe cranio-cerebral trauma. The repetitive HES doses administered in this study are the largest reported in the literature.     

The intraoperative therapeutic equivalence of balanced vs saline-based 6% hydroxyethyl starch 130/0.4 and their influence on perioperative acid-base status and renal functions

Study objectiveThis study was designed to evaluate the therapeutic equivalence of balanced 6% hydroxyethyl starch (HES) 130/0.4 (Tetraspan) vs saline-based 6% HES 130/0.4 (Voluven) regarding the volume effect and the effect on acid-base status and renal functions in patients undergoing major urologic procedures.DesignRandomized comparative trial.SettingOperating room and ward.PatientsForty patients, American Society of Anesthesiologists statuses 1 and 2.InterventionPatients were randomly allocated to receive either Voluven (n = 20) or Tetraspan (n = 20).MeasurementsHemodynamic variables. Laboratory variables in the form of arterial blood gases, serum chloride and sodium levels, hemoglobin level, international normalized ratio, and kidney and liver functions were measured after induction of anesthesia (T₁), at the end of surgery (T₂), and on the first postoperative day (T₃).Main resultsBoth groups were comparable regarding the total amount of study drugs and crystalloid consumption. No significant difference in hemoglobin levels between both groups, but there were significant differences between T₁ and T₂ hemoglobin within both groups and T₃ hemoglobin in the Tetraspan group. Both groups were comparable regarding the renal functions, but there was a significant difference between T₁ and T₂ creatinine within both groups. No significant differences between both groups in liver functions and coagulation profile, but there were significant differences between values at T₁, T₂ and T₃ within each group. Relative to baseline, both pH and bicarbonate decrease significantly in both groups. In the Voluven group, bicarbonate decreased significantly at the end of surgery relative to the Tetraspan group. Serum electrolytes did not vary between both groups.ConclusionBoth balanced 6% HES 130/0.4 (Tetraspan) and saline-based 6% HES 130/0.4 (Voluven) were equally effective for hemodynamic stabilization of patients undergoing major urologic procedures without any significant impact on acid-base status or renal functions.     

Hydroxyethyl Starch (130 kD), but Not Crystalloid Volume Support, Improves Microcirculation during Normotensive Endotoxemia

Background: Increased leukocyte-endothelial cell interaction (LE) and deterioration of capillary perfusion represent key mechanisms of septic organ dysfunction. The type of volume support, however, which may be used during septic disorders, remains controversial. Using intravital microscopy, the authors studied the effect of different regimens of clinically relevant volume support on endotoxin-induced microcirculatory disorders, including the synthetic colloid hydroxyethyl starch (HES, 130 kD) and a crystalloid regimen with isotonic saline solution (NaCl).

Methods: In Syrian Golden hamsters, normotensive endotoxemia was induced by intravenous application of Escherichia coli lipopolysaccharide (LPS, 2 mg/kg). The microcirculation was analyzed in striated muscle of skinfold preparations. HES 130 kD (Voluven(R), 16 ml/kg, n = 7) or isotonic saline (NaCl, 66 ml/kg, n = 6) were infused 3 h after LPS exposure over a 1-h period (posttreatment mode). Animals receiving LPS without volume therapy served as control subjects (n = 8, control). LE, functional capillary density (FCD), and macromolecular leakage were repeatedly analyzed in the awake animals during a 24-h period using intravital fluorescence microscopy.

Results: HES 130 kD significantly reduced LPS-induced arteriolar and venular leukocyte adherence (P < 0.05), whereas NaCl resuscitation had no effect when compared with nontreated control animals. The LPS-induced decrease in FCD and increase in macromolecular leakage were also significantly attenuated by HES 130 kD but not by NaCl. Improvement of LPS-induced microcirculatory disorders by HES was unlikely the result of macro- and microhemodynamic changes because arterial blood pressure, heart rate, and venular wall shear rate did not differ between HES- and NaCl-treated animals.     

The effect of the combined administration of colloids and lactated Ringer's solution on the coagulation system: an in vitro study using thrombelastograph coagulation analysis (ROTEG

Gelatin solutions are often given in clinical practice once the maximal dose of a median-weight hydroxyethyl starch (HES) has been reached. Colloids are usually combined with lactated Ringer's solution (RL). Whether the combined administration of colloids and/or crystalloids affects blood coagulation is not known. We diluted blood by 20%, 40%, and 60% with RL, gelatin (Gelofusin), 6% HES 130/0.4 (Voluven), and 6% HES 200/0.5 (Iso-Hes), as well as with combinations of these solutions at a ratio of 1:1 (gelatin/RL, 6% HES 130/0.4:RL, 6% HES 200/0.5:RL, 6% HES 130/0.4:gelatin, 6% HES 200/0.5:gelatin). Thereafter, blood was analyzed by using modified thrombelastograph coagulation analysis (ROTEG) and clotting time, clot formation time, and maximal clot firmness were determined. RL had the least effect on hemostasis. Gelatin administered alone impaired the coagulation system significantly less than each median-weight HES administered alone. We conclude that gelatin combined with 6% HES 200/0.5 or 6% HES 130/0.4 decreases hemostasis <6% HES 200/0.5 or 6% HES 130/0.4 administered alone. IMPLICATIONS: The effect of the combined administration of different colloids and/or crystalloids on coagulation is not known. We show that hemostasis is less impaired using a combination of gelatin and median-weight starches than using median-weight starches alone. Furthermore, the combination of lactated Ringer's solution and gelatin decreases the coagulation system to the same extent as the combination of lactated Ringer's solution and 6% hydroxyethyl starch 130/0.4.     

3.5% urea-linked gelatin is as effective as 6% HES 200/0.5 for volume management in cardiac surgery patients

PURPOSE: To compare the efficacy of volume expansion with 3.5% gelatin and 6% hydroxyethyl starch 200/0.5 in patients undergoing cardiac surgery. The second objective was to compare the two colloids in terms of blood losses and allogeneic blood transfusion exposure rate. METHODS: In this open-label controlled study, patients were randomly allocated to receive either 3.5% urea-linked gelatin (GEL group: n = 55) or 6% hydroxyethyl starch 200/0.5/5.1 (HES group: n = 55) for per- (including priming of the bypass machine) and postoperative volume management with a maximum dosage of 30 +/- 3 mL.kg(-1).day(-1). Volume replacement was guided according to routine per- and postoperative care based on cardiac index, mixed venous oxygen saturation, and diuresis. If additional colloid was required, 4.5% albumin had to be given. The study period comprised per- and postoperative investigations up to 18 hr after surgery. RESULTS: All hemodynamic variables were comparable in both groups. Total study drug was 25.8 +/- 4.8 mL.kg(-1) in the GEL group and 24.5 +/- 6.0 mL.kg(-1) in the HES group. There was no difference in the number of patients receiving albumin solution or in the amount of albumin administered. Total blood loss was higher in the HES than in the GEL group (11.0 +/- 7.8 mL.kg(-1) vs 8.7 +/- 4.0 mL.kg(-1); P < 0.05) resulting in a higher need for allogeneic blood transfusion (HES: nine patients received 12 units, GEL two patients received 3 units; P = 0.026). CONCLUSION: In the conditions of the present study, HES was not associated with a better plasma expansion effect than GEL. HES could result in a higher need for allogeneic blood transfusion.     

Plasma substitutes

Adequate restoration of intravascular volume remains an important therapeutic manoeuvre in managing the surgical, medical and the critically ill intensive care patient. Definition of the ideal volume replacement strategy still remains one of the burning problems. The choice between colloid and crystalloid solutions continues to generate controversy. The highly controversial crystalloid/colloid dispute has been enlarged to a colloid/colloid debate because aside of the natural colloid albumin several non-protein (synthetic) colloids are available as plasma substitutes (e.g. dextrans, gelatins, hydroxyethyl starch [HES] solutions). Due to their varying physico-chemical properties, these solutions widely differ with regard to their pharmacokinetic and pharmacodynamic properties as well as to their hemodynamic efficacy and side-effects. HES is the most intensively studied plasma substitute. The different HES preparations are defined by concentration, molar substitution (MS), mean molecular weight (MW), and the C2/C6 ratio of substitution. Two new HES specification, a third-generation HES with a lower Mw and a lower MS (6% HES 130/0.4) than all other HES preparation and a first-generation HES prepared in a balanced solution, may be promising by improving the therapy of the hypovolemic patient. Albumin cannot be recommended for correction of hypovolemia because of ist extreme costs and because it can easily be replaced by other no-protein colloids. Dextrans should also not be used any more due to the negative effects on coagulation and its high anaphylactic potency. The historical crystalloid/colloid controversy has been focused primarily on outcome. There is increasing evidence that outcome (mortality) is not the correct measure when assessing the ideal volume replacement strategy. New concepts about critical care such as organ perfusion and organ function, the role of inflammation, immunological aspects, and wound healing may change this point of view. Volume replacement has been hitherto often based on art, dogma and personal beliefs. Further well-performed studies in this area will help more to shed new light on the ideal volume replacement strategy of the hypovolemic patient than more meta-analyses that are pooling old-to-very old studies to solve this problem.     

Hydroxyethyl starch 130/0.4 versus modified fluid gelatin for volume expansion in cardiac surgery patients: the effects on perioperative bleeding and transfusion needs

In this prospective, randomized, open controlled study we compared the effects on net red blood cell loss of 6% hydroxyethyl starch 130/0.4 (HES: n = 64) and 3% modified fluid gelatin (GEL: n = 68) administered for intravascular volume management in patients undergoing coronary surgery. Blood losses were calculated from determination of circulating blood volume and measurement of preoperative and postoperative hematocrit. Amount of colloids that could be administered was limited to 50 mL/kg. If additional fluids were required, balanced crystalloid solution was used. Anesthetic and surgical techniques were standardized. Both groups were similar with regard to demographic and intraoperative variables. Total study drug was 48.9 +/- 17.2 mL/kg in the HES group and 48.9 +/- 14.6 mL/kg in the GEL group. Total red blood cell loss was 544 +/- 305 mL in the HES group and 504 +/- 327 mL the GEL group. Measured blood losses were also similar in both groups (HES, 19.4 +/- 12.3 mL/kg; GEL, 19.2 +/- 14.5 mL/kg). Exposure to allogeneic blood product was comparable in both groups. In the conditions of the present study, HES 130/0.4 up to 50 mL/kg is a valuable alternative to modified fluid gelatin for plasma volume expansion during and after cardiac surgery.